This application addresses the broad Challenge Area (13) Smart Biomaterials - Theranostics and the specific Challenge Topic, 13-DE-102: Dental Resin Composites and Caries. With a majority of the more than 100,000 million dental restorative treatments performed in the US each year involving the placement of resin-bonded composite materials, and the observation from NIH/NIDCR that a large portion of a dentist's time is consumed with replacing these restorations, there is a clear need for materials with improved clinical performance. Composite restoratives not only hold an esthetic advantage over dental amalgams, but they offer a means to adhesively bond the restoration to dentin and enamel. However, due to polymerization shrinkage stresses that challenge this critical interface from the time of placement and a well-recognized weakening of the hydrophilic adhesive layer with prolonged exposure to the aqueous oral environment, a strong, intact margin can not currently be reliably obtained. This situation is being exacerbated by the shift towards self-etching one-step adhesives which while providing greater convenience to the practitioner, have proven to be even less reliable than the two-step etch and rinse adhesive systems. Since a high percentage of the problems in restorations requiring replacement are linked to marginal degradation, marginal staining and secondary caries formed at the margins, this appears to be great need for a substantially improved dental adhesive that can offer significantly greater initial strength and most importantly, the retention of that strength and sealing ability long term in the oral environment. A highly versatile technique has been developed recently for preparing nano- scale (5 - 100 nm) polymeric particles with control over branching, chemistry and reactive site placement. These reactive nanogels can be dispersed readily in high concentration in secondary monomers which then infiltrate and copolymerize with the prepolymer additives. This approach has provided dramatic reductions in polymerization shrinkage and stress, as well as a demonstrated ability to improve the strength of a model dental adhesive resin and then maintain that strength after complete water equilibration. There is no reasonable alternative to the use of hydrophilic monomers in dental adhesive materials since these resins must be able to penetrate well into the dentinal tubules and demineralized dentin which always retains significant moisture content. The nanogel particles can be designed to be moderately to extremely hydrophobic while also providing a high modulus network structure that has little effect on viscosity of the matrix monomer. The nanogel surface, which includes polymerizable groups to covalently attach to the matrix polymer, can also be modified with a hydrophilic shell that allows great affinity for the matrix monomer as well as the dentin substrate. The proposed project would validate the positive preliminary results and within two years, it can be expected that this new technology could be generically incorporated in to a wide variety of traditional dental adhesive materials with the result that stronger, more reliable bonded restorations could be available. There are over 100 million dental restorations placed in the US each year and most of these are resin-bonded composite materials which have good initial strength and esthetics but also a high failure/replacement rate. A primary reason for these revisions is the deterioration of the adhesive integrity which allows bacterial leakage, staining, and potentially the onset of new decay in the compromised tooth. Because of the very large numbers, the predicted significant improvements in adhesive strength and long-term reliability will generate a substantial return in fewer patient visits and expensive replacement procedures as well as improved overall oral health.